Tetradehydrohalicyclamine B, a new proteasome inhibitor from the marine sponge Acanthostrongylophora ingens

Bioorg Med Chem Lett. 2019 Jan 1;29(1):8-10. doi: 10.1016/j.bmcl.2018.11.028. Epub 2018 Nov 14.

Abstract

A new halicyclamine derivative, tetradehydrohalicyclamine B (1), was isolated from the marine sponge Acanthostrongylophora ingens, along with halicyclamine B (2) as proteasome inhibitors. Compound 1 is the second example found to have a pyridinium ring in the halicyclamine family. Although the relative configuration of 2 was previously determined by X-ray crystallographic analysis, here we determined the absolute configuration of 2 by ECD experiment. Compounds 1 and 2 inhibited the constitutive proteasome as well as the immunoproteasome. The inhibitory activities of 2 were 4- to 10-fold more potent than those of 1.

Keywords: Acanthostrongylophora ingens; Constitutive proteasome; Halicyclamine; Immunoproteasome; Proteasome inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification
  • Depsipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Models, Molecular
  • Molecular Structure
  • Porifera / chemistry*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors / chemistry
  • Proteasome Inhibitors / isolation & purification
  • Proteasome Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Depsipeptides
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex